Solid-phase microextraction for assessment of plasma protein binding, a complement to rapid equilibrium dialysis.

Determination of plasma protein binding () is considered vital for better understanding of pharmacokinetic and pharmacodynamic activities of drugs due to the role of free concentration in pharmacological response. Solid-phase microextraction (SPME) was investigated for measurement of from biological matrices and compared with a gold standard approach (rapid equilibrium dialysis [RED]). SPME-derived values of correlated well with literature values, and those determined by RED.

Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives.

A simple synthetic route affording 27%-85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The ¹H- and (13)C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra.

Small molecule recognition of mephedrone using an anthracene molecular clip.

An anthracene molecular probe has been synthesised and shown to target mephedrone, a stimulant drug from the cathinone class of new psychoactive substances (NPS). A protocol has been developed to detect mephedrone via the probe using NMR spectroscopy in a simulated street sample containing two of the most common cutting agents, benzocaine and caffeine.

[The origin of a differentiated neuropsychopharmacotherapy for children and adolescents: an analysis of psycho- and neuropharmacology in the 1940s and 50s].

Objective: The origin of a differentiated approach to neuropsychopharmacotherapy in children and adolescents can be traced back to the 1940s and 50s. Certain clinical disorders in the range of psychiatry and neurology were treated with a multiplicity of substances.

Method: We conducted an exclusive screening of 700 medical records of patients under 18 years of age from a psychiatric university hospital in Jena (from 1942–1945) and 89 files of children who attended Trüper’s approved school in Jena between 1946 and 1954.

Association between methadone dose and concomitant cocaine use in methadone maintenance treatment: a register-based study.

Background: Concomitant cocaine use is a major problem in clinical practice in methadone maintenance treatment (MMT) and may interfere with successful treatment. Data from European methadone populations is sparse. This register-based study sought to explore the association between prescribed methadone dose and concomitant cocaine and heroin use in the methadone population of Basel City.

Direct ionization of solid-phase microextraction fibers for quantitative drug bioanalysis: from peripheral circulation to mass spectrometry detection.

A novel approach is described for the quantitative bioanalysis of drugs in blood samples by ionization of the analytes collected on solid-phase microextraction (SPME) fibers by mass spectrometry (MS). The technique combines the attractive features of SPME microsampling using minimal sample volumes with the speed, selectivity, and sensitivity capabilities of MS detection. The method reported in this study involved generating gas-phase ions directly from SPME fibers without the need for any additional sample preparation or chromatographic separation; the entire process was completed within 5 min.

Acute effects of heroin on emotions in heroin-dependent patients.

Background: Euphoria has been described in heroin-dependent individuals after heroin administration. However, affective disturbances and disorders are common in heroin dependence. The present study examined the acute effects of heroin on emotions in heroin-dependent patients.

The impact of diacetylmorphine on hypothalamic-pituitary-adrenal axis activity and heroin craving in heroin dependence.

Background/aim: Heroin dependence is a chronic relapsing disorder characterized by the compulsion to seek and use heroin. Stress and craving are seen as key factors for heroin use. Moreover, altered hypothalamic-pituitary-adrenal (HPA) axis function has been frequently reported.

The lack of negative affects as an indicator for identity disturbance in borderline personality disorder: a preliminary report.

Background: Patients with borderline personality disorder (BPD) suffer from instability of their relationships, their affectivity and their identity. The purpose of the study was to investigate negative affects and identity disturbance in patients with BPD and in patients without personality disorder using questionnaire data and interview data.

Sampling And Methods: Twelve patients with BPD and 12 patients with major depressive disorder without any personality disorder were assessed with the Structured Interview of Personality Organization (STIPO) and questionnaires (Inventory of Personality Organization, Beck Depression Inventory, State-Trait Anxiety Inventory).

[Johannes Trüper--mediator between child and adolescent psychiatry and pedagogy].

Objective: The development of the child and adolescent psychiatry as an independent speciality is not only a result of sub-specialisation within medicine or psychiatry but also a result of interaction with pedagogy, psychology, and philosophy. Within this framework, pedagogy (and more specifically orthopedagogy) has played an essential scientific role. This will be demonstrated by the work of Johannes Trüper.

Exploring a chemical encoding strategy for combinatorial synthesis using Friedel-Crafts alkylation.

The use of scandium(III) triflate and ytterbium(III) triflate-catalysed Friedel-Crafts alkylation to insert a set of hydroxymethyl pyrrole amide tags (1b-i) on to polystyrene resins under mild conditions and the encoding of a split and mix peptide library is demonstrated.

Endophenotype properties of niacin sensitivity as marker of impaired prostaglandin signalling in schizophrenia.

Background: Disruption of arachidonic acid pathways and prostaglandin signalling has been implicated in the pathophysiology of schizophrenia.

Aims: We intended to study prostaglandin signalling in groups of young schizophrenia patients, first-degree relatives, and healthy controls in order to assess effects of heritability on this biological marker-one important endophenotype criterion.

Method: Namely, we assessed intensity of methylnicotinate skin flushing using optical reflection spectroscopy.

[Rudolf Lemke's contribution to the development of child neuropsychiatry in Jena, Germany].

Child and adolescent psychiatry has a long tradition in Jena, Germany, and goes back to the psychiatrists Theodor Ziehen and Wilhelm Strohmayer. It seems that Rudolf Lemke (1906-1957) eminently promoted the development of child and adolescent psychiatry after World War II. A versatile scientist, Lemke had many publications in psychiatric and neurologic fields.

Social factors but not stress-coping styles predict relapse in detoxified alcoholics.

Alcohol-dependent patients face a substantial risk of relapse after detoxification. Though psychosocial stress and coping strategies are regarded as major contributing factors in returning to drinking, the direct effects of coping styles on relapse are not clear. In this treatment outcome study, a mixed gender sample of 130 detoxified and well-characterized alcohol-dependent patients (37 women) was followed up over a period of 12 months after 6 weeks of inpatient treatment.

Controlled study on the combined effect of alcohol and tobacco smoking on testosterone in alcohol-dependent men.

Aims: The present study examined the association between pre-treatment drinking and smoking parameters and plasma testosterone levels before and after alcohol withdrawal.

Methods: A total of 51 alcohol-dependent men and 43 age-matched healthy men were investigated. In alcoholics, free testosterone in plasma was measured on the day of admission, after detoxification and after 6 weeks of sobriety.

Changes of pain perception, autonomic function, and endocrine parameters during treatment of anorectic adolescents.

Objectives: The underlying mechanisms of reduced pain perception in anorexia nervosa (AN) are unknown. To gain more insight into the pathology, the authors investigated pain perception, autonomic function, and endocrine parameters before and during successful treatment of adolescent AN patients.

Method: Heat pain perception was assessed in 15 female adolescent AN patients and matched controls.

Cortisol concentrations, stress-coping styles after withdrawal and long-term abstinence in alcohol dependence.

Alcohol-dependent patients face a substantial risk of relapse after detoxification. A major risk factor for relapse is stress which is reflected biologically by various physiological changes that include an activation of the hypothalamic-pituitary-adrenal (HPA) axis and release of glucocorticoids. The prospective study examined cortisol concentrations and stress-coping styles in relation to abstinence 1 year following discharge from treatment.

NK1 antagonists based on seven membered lactam scaffolds.

A new class of high affinity hNK1R antagonists based on seven-membered ring cores has been identified. This series, with relatively simple, compact structures, includes compounds with high affinity, good selectivity, and promising in vivo properties.

A new pyridazine series of GABAA alpha5 ligands.

Screening of the Merck compound collection identified 6 as an unusually simple, low molecular weight hit with moderate affinity for GABAA receptors. The structural novelty of 6, compared to our advanced series of GABAA alpha5 inverse agonists, made it an attractive molecule for further exploration. This paper will describe the evolution of 6 into a new series of ligands with nanomolar affinity and functional selectivity for GABAA alpha5 receptor subtypes.

1H NMR study of the conformation and absolute stereochemistry of two spirocyclic NK-1 antagonists.

The binding affinities at the human NK-1 receptor of two spirocyclic compounds were found to be similar despite being epimeric at a key stereocentre. This unexpected result prompted a thorough investigation of the solution conformations of the two compounds. This revealed that a conformational switch in the tetrahydrofuran ring enabled the C-3-aryl group to be equatorial in both cases, leading to a similar juxtaposition of the aryl rings.

Aryl sulfones: a new class of gamma-secretase inhibitors.

The development of a novel series of 4-aryl, 4-phenylsulfonyl cyclohexananone-derived gamma-secretase inhibitors for the potential treatment of Alzheimer's disease is described.

["If Berger had survived the second world war - he certainly would have been a candidate for the Nobel Prize". Hans Berger and the legend of the Nobel Prize].

The public opinion pays much attention to the Nobel Prize as an indicator for the scientific efficiency of a university or a country in connection with foundation of so-called elite universities. The former holder of the psychiatric chair in Jena and discoverer of the electroencephalogram Hans Berger (1873 - 1941) came into discussion as candidate for the Nobel Prize in physiology or medicine. The current medical-historical publications maintain the view that Berger should have received the Nobel Prize in 1936 as well as in 1949.

Open-access high-resolution mass spectrometry in early drug discovery.

Techniques such as mass spectrometry and NMR spectroscopy form an essential part of the medicinal chemist's toolbox for characterizing and assessing the purity of new molecules. Empowering medicinal chemists to gain early insight into their reaction products has a direct impact on productivity. Devolution of cutting-edge techniques from the specialist to the bench chemist also frees the specialist to concentrate on solving the more demanding of analytical problems.

Accelerated metabolite identification by "extraction-NMR".

Examples of the use of extraction-NMR, an efficient and rapid method to obtain structural information on metabolites without prior separation, are described. Crude ethyl acetate extracts of in vitro microsomal incubations were analysed by NMR spectroscopy. The region downfield of 5.